scholarly journals 5,6-Dichloro-2-Phenyl-Benzotriazoles: New Potent Inhibitors of Orthohantavirus

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 122 ◽  
Author(s):  
Giuseppina Sanna ◽  
Sandra Piras ◽  
Silvia Madeddu ◽  
Bernardetta Busonera ◽  
Boris Klempa ◽  
...  
Keyword(s):  
Rna Virus ◽  
Hemorrhagic Fever ◽  
Hantaan Virus ◽  
Reduction Assay ◽  
Antiviral Activities ◽  
Syncytial Virus ◽  
Focus Reduction ◽  
Approved Drugs ◽  
Reservoir Hosts ◽  
Fda Approved Drugs

Orthohantaviruses, previously known as hantaviruses (family Hantaviridae, order Bunyavirales), are emerging zoonoses hosted by different rodent and insectivore species. Orthohantaviruses are transmitted by aerosolized excreta (urine, saliva and feces) of their reservoir hosts. When transmitted to humans, they cause hemorrhagic fever with renal syndrome (HFRS) in Asia and Europe and hantavirus (cardio) pulmonary syndrome (HPS) in the Americas. Clinical studies have shown that early treatments of HFRS patients with ribavirin (RBV) improve prognosis. Nevertheless, there is the need for urgent development of specific antiviral drugs. In the search for new RNA virus inhibitors, we recently identified a series of variously substituted 5,6-dichloro-1(2)-phenyl-1(2)H-benzo[d][1,2,3]triazole derivatives active against the human respiratory syncytial virus (HRSV). Interestingly, several 2-phenyl-benzotriazoles resulted in fairly potent inhibitors of the Hantaan virus in a chemiluminescence focus reduction assay (C-FRA) showing an EC50 = 4–5 µM, ten-fold more active than ribavirin. Currently, there are no FDA approved drugs for the treatment of orthohantavirus infections. Antiviral activities and cytotoxicity profiles suggest that 5,6-dichloro-1(2)-phenyl-1(2)H-benzo[d][1,2,3]triazoles could be promising candidates for further investigation as a potential treatment of hantaviral diseases.

Mechanisms of Action of Ribavirin in Antiviral Therapies

2001 ◽  
Vol 12 (5) ◽  
pp. 261-272 ◽  
Author(s):  
Robert C Tam ◽  
Johnson YN Lau ◽  
Zhi Hong
Keyword(s):  
Hepatitis C ◽  
Viral Infections ◽  
Rna Virus ◽  
Lassa Fever ◽  
Biological Properties ◽  
Interferon Α ◽  
Hepatitis C Infection ◽  
Antiviral Activities ◽  
Syncytial Virus

Although ribavirin was originally synthesized over 30 years ago and has been used to treat viral infections as monotherapy (respiratory syncytial virus and Lassa fever virus) or with interferon-α (IFN-α) as combination therapy (hepatitis C virus), the precise mechanism of its therapeutic activities remains controversial. In this review we focus on two main biological properties of ribavirin: its indirect and direct antiviral activities (with particular emphasis on its efficacy against chronic hepatitis C infection). Each property could individually or collectively account for its clinical efficacy against viral infections. First, with emphasis on the evidence for indirect activities of ribavirin, we will review the clinical observations that suggest that the immunomodulatory properties of ribavirin can in part account for its antiviral activities in vivo. We will then describe the mode of ribavirin's direct antiviral activities. These direct activities can be ascribed to several possible mechanisms, including the recently described activity as an RNA mutagen, a property that may be important in driving a rapidly mutating RNA virus over the threshold to ‘error catastrophe′.

scholarly journals COVID-19: disease pathways and gene expression changes predict methylprednisolone can improve out- come in severe cases

2020 ◽  
Author(s):  
Sorin Draghici ◽  
Tuan-Minh Nguyen ◽  
Larry A. Sonna ◽  
Cordelia Ziraldo ◽  
Radu Vanciu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Influenza A ◽  
Immune Modulation ◽  
Clinical Results ◽  
Current Management ◽  
All Cause Mortality ◽  
Syncytial Virus ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Disease Pathways

Abstract Current management efforts of COVID-19 include: early diagnosis, use of antivirals, and immune modulation. After the initial viral phase of the illness, identification of the patients developing cytokine storm syndrome is critical.1, 2 Treatment of hyper- inflammation in these patients using existing, approved therapies with proven safety profiles could address the immediate need to reduce the rising mortality.3 The identification of existing drugs that could modulate the immune response is an immediate need. Here we show that an analysis of the changes in the gene expression, path- ways and putative mechanisms between SARS-CoV2, influenza A, and respiratory syncytial virus can be used to identify FDA-approved drugs that could be repurposed to help COVID-19 patients with severe symptoms related to hyper-inflammation. An important finding is that drugs in the same class may not achieve similar effects. An independent clinical study evaluated 213 subjects, 81 (38%) and 132 (62%) in pre-and post-methylprednisolone groups, respectively. Thirty-day all-cause mortality occurred at a significantly lower rate in the post-methylprednisolone group compared to pre-methylprednisolone group (29.6% vs. 16.6%, p=0.027). Clinical results con- firmed the in silico prediction that methylprednisolone could improve outcomes in severe cases of COVID-19. These findings are important for any future pandemic regardless of the virus.

Phytochemicals as Potential Curative Agents against Viral Infection: A Review

2020 ◽  
Vol 24 (20) ◽  
pp. 2356-2366
Author(s):  
Abhijeet Kumar ◽  
Anil Kumar Singh ◽  
Garima Tripathi
Keyword(s):  
Natural Products ◽  
Therapeutic Agents ◽  
Pharmacological Activities ◽  
Diverse Range ◽  
Current Health ◽  
Antiviral Activities ◽  
Approved Drugs ◽  
Novel Drug ◽  
Fda Approved Drugs ◽  
New Chemical Entity

The present pandemic erupted due to highly contagious coronavirus SARS-CoV- 2, and lack of any efficient therapy to restrain its infection and treatment, led the scientific community to re-evaluate the efficacy of commonly available phytochemicals as potential therapeutic agents. The vast pharmacological activities and medicinal significance of the plant-derived natural products against a diverse range of physiological disorders and diseases are well documented. Under the current health emergency across the world, there is an urgent requirement of repurposing of the available FDA approved drugs and natural products which could help in controlling the infections and alleviating the severity of the diseases as discovering entirely new chemical entity as a novel drug would be a protracted and costly journey. Some of the phytochemicals have already displayed potential anti-viral activity against different targets of SARS-CoV-2 virus. The present review would provide an account of the prevalent phytochemicals with antiviral activities, which would help in the development of promising drug therapy for the treatment of COVID-19 and similar such highly infectious viruses.

scholarly journals Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs

2020 ◽  
Author(s):  
Sangeun Jeon ◽  
Meehyun Ko ◽  
Jihye Lee ◽  
Inhee Choi ◽  
Soo Young Byun ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Drug Repositioning ◽  
Antiviral Drug ◽  
Drug Candidates ◽  
Global Challenge ◽  
Feasible Option ◽  
Antiviral Activities ◽  
Approved Drugs ◽  
Near Future ◽  
Fda Approved Drugs

AbstractCOVID-19 is an emerging infectious disease and was recently declared as a pandemic by WHO. Currently, there is no vaccine or therapeutic available for this disease. Drug repositioning represents the only feasible option to address this global challenge and a panel of 48 FDA-approved drugs that have been pre-selected by an assay of SARS-CoV was screened to identify potential antiviral drug candidates against SARS-CoV-2 infection. We found a total of 24 drugs which exhibited antiviral efficacy (0.1 μM < IC50 < 10 μM) against SARS-CoV-2. In particular, two FDA-approved drugs - niclosamide and ciclesonide – were notable in some respects. These drugs will be tested in an appropriate animal model for their antiviral activities. In near future, these already FDA-approved drugs could be further developed following clinical trials in order to provide additional therapeutic options for patients with COVID-19.

scholarly journals REASON FOR USING IVERMECTIN IN COVID-19-A REVIEW

2020 ◽  
pp. 77-78
Author(s):  
J. Jayasheela ◽  
G. Somasundaram ◽  
DS. Disha Sheoran
Keyword(s):  
Rna Virus ◽  
Polymerase Chain Reaction Test ◽  
Parasitic Infections ◽  
Nasopharyngeal Swab ◽  
Polymerase Chain ◽  
Approved Drugs ◽  
Tract Infections ◽  
Chain Reaction Test ◽  
Fda Approved Drugs

COVID-19 is an emerging, rapidly evolving situation worldwide. It is a contagious respiratory disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) which spreads through air (droplet infection) when an infected person sneezes or coughs. The SARS CoV-2 is a 50 nm, positive sense single stranded RNA virus and it is diagnosed from a nasopharyngeal swab by real-time Reverse Transcriptase Polymerase Chain Reaction test (RT-PCR). It produces symptoms like fever, fatigue, dry cough, breathing difficulties and loss of smell and taste. It can cause both Upper and Lower Respiratory tract infections. Although there are many clinical trials going on worldwide to test possible therapies there are a few older, FDA approved drugs that can fight COVID-19. One of these drugs is Ivermectin, used to treat parasitic infections. It has in vitro antiviral effects and has shown to inhibit replication in SARS CoV-2. Ivermectin is a safe, FDA approved drug which has high efficacy. Therefore, it could serve as potential treatment for mild to moderate SARS CoV-2 infections.

scholarly journals Screening of FDA-approved Drugs and Identification of Novel Lassa Virus Entry Inhibitors

2018 ◽  
Author(s):  
Peilin Wang ◽  
Yang Liu ◽  
Guangshun Zhang ◽  
Shaobo Wang ◽  
Jiao Guo ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Transmembrane Domain ◽  
Hemorrhagic Fever ◽  
Mechanistic Study ◽  
Lassa Virus ◽  
Entry Inhibitors ◽  
Glycoprotein Complex ◽  
Virus Entry Inhibitors ◽  
Approved Drugs ◽  
Fda Approved Drugs

ABSTRACTLassa virus (LASV) belongs to the Mammarenavirus genus (family Arenaviridae) and causes severe hemorrhagic fever in humans. At present, there are no Food and Drug Administration (FDA)-approved drugs or vaccines specific for LASV. Herein, high-throughput screening of an FDA-approved drug library was performed against LASV entry using a pseudo-type virus enveloping LASV glycoproteins. Two hit drugs, lacidipine and phenothrin, were identified as LASV entry inhibitors in the micromolar range. A mechanistic study revealed that both drugs inhibited LASV entry by blocking low-pH-induced membrane fusion. Moreover, lacidipine irreversibly bound to the LASV glycoprotein complex (GPC), resulting in virucidal activity. Adaptive mutant analyses demonstrated that replacement of T40, located in the ectodomain of the stable-signal peptide (SSP), with lysine (K) conferred LASV resistance to lacidipine without apparent loss of the viral growth profile. Furthermore, lacidipine showed antiviral activity and specificity against both LASV and the Guanarito virus (GTOV), which is also a category A new world arenavirus. Drug-resistant variants indicate that the V36M in ectodomain of SSP mutant and V436A in the transmembrane domain of GP2 mutant conferred GTOV resistance to lacidipine, suggesting that lacidipine might act via a novel mechanism other than calcium inhibition. This study shows that both lacidipine and phenothrin are candidates for LASV therapy, and the membrane-proximal external region of the GPC might provide an entry-targeted platform for inhibitors.

Phytochemicals as Potential Curative Agents against Viral Infection: A Review

2020 ◽  
Vol 24 (20) ◽  
pp. 2356-2366
Author(s):  
Abhijeet Kumar ◽  
Anil Kumar Singh ◽  
Garima Tripathi
Keyword(s):  
Natural Products ◽  
Therapeutic Agents ◽  
Pharmacological Activities ◽  
Diverse Range ◽  
Current Health ◽  
Antiviral Activities ◽  
Approved Drugs ◽  
Novel Drug ◽  
Fda Approved Drugs ◽  
New Chemical Entity

The present pandemic erupted due to highly contagious coronavirus SARS-CoV- 2, and lack of any efficient therapy to restrain its infection and treatment, led the scientific community to re-evaluate the efficacy of commonly available phytochemicals as potential therapeutic agents. The vast pharmacological activities and medicinal significance of the plant-derived natural products against a diverse range of physiological disorders and diseases are well documented. Under the current health emergency across the world, there is an urgent requirement of repurposing of the available FDA approved drugs and natural products which could help in controlling the infections and alleviating the severity of the diseases as discovering entirely new chemical entity as a novel drug would be a protracted and costly journey. Some of the phytochemicals have already displayed potential anti-viral activity against different targets of SARS-CoV-2 virus. The present review would provide an account of the prevalent phytochemicals with antiviral activities, which would help in the development of promising drug therapy for the treatment of COVID-19 and similar such highly infectious viruses.

Thiazole Compounds as Antiviral Agents: An Update

2020 ◽  
Vol 16 (1) ◽  
pp. 4-23 ◽  
Author(s):  
Inder P. Singh ◽  
Shiv Gupta ◽  
Sanjay Kumar
Keyword(s):  
Biological Activities ◽  
Relevant Literature ◽  
Antiviral Agents ◽  
Experimental Drugs ◽  
Patent Literature ◽  
Antiviral Activities ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Anti Hiv ◽  
Hiv 1

Background: Thiazole is a good nucleus owing to its various pharmaceutical applications. Thiazole containing compounds (thiazoles) have shown various biological activities like antioxidant, analgesic, antibacterial, anticancer, antiallergic, antihypertensive, antiinflammatory, antimalarial, antifungal and antipsychotic. The scaffold is present in more than 18 FDA approved drugs and also in more than 70 experimental drugs. Only a few reviews are available in the literature despite its great medicinal importance. During the course of time, this scaffold has been studied extensively for its antiviral activities and provided compounds with activity in the nM range. However, no focused review is available on the compilation of antiviral activities shown by this scaffold. Objective: In the present review, we have made an effort to compile antiviral literature of thiazoles reported from the year 2011 to till date. Methods: We searched the SciFinder database (excluding patent literature) with keywords like “antiviral”, “anti-HIV” and “virus”. Further filters were applied for the year of publication and keywords thiazole, reviews etc. to find relevant literature reported on the antiviral activities of thiazoles. Results: Nearly, 50 research articles were selected to compile and review the antiviral literature of thiazoles reported from the year 2011 to till date. Compounds 8, 25, 40, 62, 72, 73, 91, 112, 113, 131, 137, 175, 198, 200, 201 and 213 were reported in the literature with potent antiviral activity against CVB, SARS, RSV, HCV, HRV, VZV, TMV, FMDV, DENV, YFV, influenza virus, Junin virus, HIV-1, HSV, VV and EBV, respectively. Conclusion: There is further scope for the synthesis and evaluation of novel thiazole compounds by taking the most active compounds as lead structures. In conclusion, this review provides an overview of antiviral activities of thiazole compounds reported from the year 2011 to till date.

scholarly journals Integrative Analysis of HTNV Glycoprotein Derived MHC II Epitopes by In Silico Prediction and Experimental Validation

2021 ◽  
Vol 11 ◽  
Author(s):  
Hao Sun ◽  
Zhenhua Lu ◽  
Guoyun Xuan ◽  
Ning Liu ◽  
Tianhu Wang ◽  
...  
Keyword(s):  
In Silico ◽  
Rna Virus ◽  
Large Population ◽  
Hemorrhagic Fever ◽  
Hantaan Virus ◽  
Class I Mhc ◽  
Mhc I ◽  
Mhc Ii ◽  
Host Virus Interactions ◽  
Virus Interactions

Hantaan virus (HTNV), the causative pathogen of hemorrhagic fever with renal syndrome (HFRS), is a negative RNA virus belonging to the Orthohantaviridae family. HTNV envelope glycoprotein (GP), encoded by the genomic medium segment, is immunogenic and is therefore a promising vaccine candidate. Major histocompatibility complex class I (MHC-I) epitopes derived from HTNV has been extensively studied, but little is known of MHC-II epitopes. In silico predictions based on four databases indicated that the full-length HTNV GP has 1121 15-mer epitopes, of which 289 had a high score for binding to the human and murine MHC-II superfamily. It found that epitope ILTVLKFIANIFHTS could potentially bind most MHC-II molecules covering human and murine haplotypes. Dominant epitopes were validated by enzyme-linked immunospot assay of splenocytes from immunized mice; 6 of 10 epitopes supported the predictions including TATYSIVGPANAKVP, TKTLVIGQCIYTITS, FSLLPGVAHSIAVEL, CETYKELKAHGVSCP, CGLYLDRLKPVGSAY, and NLGENPCKIGLQTSS. Conservation analysis of dominant epitopes revealed host–virus interactions without geographic stratification, thus meeting the requirements of candidate vaccines for large-population prophylaxis. These findings provide insight into hantavirus antigenicity and suggest that vaccines targeting MHC-II could provide immune protection in large population to complement symptomatic therapies for the treatment of HFRS.

scholarly journals Hantaan Virus Infection Induces CXCL10 Expression through TLR3, RIG-I, and MDA-5 Pathways Correlated with the Disease Severity

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Yusi Zhang ◽  
Bei Liu ◽  
Ying Ma ◽  
Jing Yi ◽  
Chunmei Zhang ◽  
...  
Keyword(s):  
Immune Response ◽  
Transcription Factors ◽  
Virus Infection ◽  
Inflammatory Responses ◽  
Rna Virus ◽  
Hemorrhagic Fever ◽  
Molecular Regulation ◽  
Hantaan Virus ◽  
Regulation Mechanism

Hantaan virus (HTNV) is a major agent causing hemorrhagic fever with renal syndrome (HFRS). Although the pathogenesis of HFRS is unclear, some reports have suggested that the abundant production of proinflammatory cytokines and uncontrolled inflammatory responses may contribute to the development of HFRS. CXCL10 is one of these cytokines and is found to be involved in the pathogenesis of many virus infectious diseases. However, the role of CXCL10 in the pathogenesis of HFRS and the molecular regulation mechanism of CXCL10 in HTNV infection remain unknown. In this study, we report that CXCL10 expresses highly in the HFRS patients’ sera and the elevated CXCL10 is positively correlated with the severity of HFRS. We find that HTNV, a single-strand RNA virus, can act as a double-strand RNA to activate the TLR3, RIG-I, and MDA-5 signaling pathways. Through the downstream transcription factors of these pathways, NF-κB and IRF7, which bind directly to the CXCL10’s promoter, the expression of CXCL10 is increased. Our results may help to better understand the role of CXCL10 in the development of HFRS and may provide some novel insights into the immune response of HTNV infection.

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